Prediction of Residual Disease by Circulating DNA Detection After Potentiated Radiotherapy for Locally Advanced Head and Neck Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 63
- 试验地点
- 8
- 主要终点
- Rate of patients with incomplete cervical lymph node response on PET-CT after radiochemotherapy having circulating DNA (cDNA)
研究概览
简要总结
Sixty percent of newly diagnosed head and neck squamous cell carcinomas (HNSCCs) are at a locally advanced (LA) stage. Depending on tumor site, stage, and resectability, locoregional failure rates can range from 35% to 65%. The persistence of residual disease at the end of treatment is a major prognostic element but is not always reliably assessed by current imaging techniques. Up to 40-50% of patients have residual adenomegaly and only 30% have viable disease when further adenectomy is performed. Sensitive and reproducible detection of residual disease after treatment is a major challenge in this patient category.
18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) guided surveillance, with a negative predictive value of 95-97%, has proven to be non-inferior to cervical curage in HNSCCs with residual adenomegaly. Cervical curage is now indicated only if the response assessed by PET-CT is incomplete. Nevertheless, the ability of PET-CT to predict treatment failure is unsatisfactory due to a high frequency of false positives, because of inflammatory changes, with a positive predictive value of about 20-50%.
Circulating tumor DNA (ctDNA) may provide a more reliable assessment of response to potentiated radiotherapy. Liquid biopsy monitoring of response in patients treated with potentiated radiation therapy for locally advanced HNSCCs a has been shown to be feasible. In 85% of patients, ctDNA is detectable and correlates significantly with tumor volume and response to treatment. In addition, one study showed that post-radiotherapy analysis of circulating HPV16 viral DNA (cvDNA) in patients with HPV16-related HNSCCs complemented PET-CT and helped guide management decisions. HPV16 cvDNA and PET-CT have similar negative predictive values, whereas the positive predictive value is higher for HPV16 cvDNA (100% versus 50%). Nevertheless, current data are insufficient to allow routine use of this marker.
This is a multicenter, single arm, open study for patients with a locally advanced head and neck cancer for which a potentiated radiotherapy is indicated.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years and ≤ 80 years
- •Histologically confirmed, never treated squamous cell carcinoma with lymph node involvement
- •squamous cell carcinoma p16+or p16-, stage III (N1), IVa or IVb (UICC classification 8th edition), N1 minimum, and oropharyngeal sqamous cell carcinomas p16+ stage I or II, N1 minimum, resectable but not operated or unresectable, with indication for concomitant or sequential radiochemotherapy with induction chemotherapy using Docetaxel, Platinum, 5-Fluorouracil (TPF or modified TPF according to the practices of the investigating centers)
- •Oral cavity, oropharynx, hypopharynx or larynx, cervical adenopathies without primary
- •Availability of FFPE samples prior to treatment initiation
- •Detection of circulating DNA in the initial blood sample
- •Obtaining informed consent from the patient
- •Affiliation to the French social security system
排除标准
- •Tumor of the nasopharynx, sinuses, nasal cavity, salivary glands or thyroid cancer
- •Treatment by exclusive radiotherapy
- •Contraindication to cervical lymph node dissection
- •Metastatic disease (stage IVc)
- •Previous treatment for head and neck cancer
- •History of other cancer in the last 3 years (except carcinoma in situ, basal cell skin carcinoma, localized prostate cancer Gleason 6)
- •Pregnant or breastfeeding woman
- •Patient under guardianship or curators
- •Psychological disorder (cognitive disorders, vigilance disorders, etc.) or social reasons (deprivation of liberty by judicial or administrative decision) or geographical reasons that could compromise the medical follow-up of the trial or compliance with the treatment
研究组 & 干预措施
Interventional
干预措施: Blood sample (Biological)
结局指标
主要结局
Rate of patients with incomplete cervical lymph node response on PET-CT after radiochemotherapy having circulating DNA (cDNA)
时间窗: 3 months after potentiated radiotherapy
Presence/absence of circulating DNA after treatment versus presence/absence of residual disease
次要结局
- Assessment of the prognosis value of the presence of residual adenomegaly(At month 27)
- Rate of concordance of mutational profiles and Human papillomavirus-high risk (HPV-HR) genotypes between the primary tumor and cDNAs at diagnosis(Inclusion)
- Rate of concordance between p16 immunohistochemistry and HPV-HR genotyping on the primary tumor(Inclusion)
- Test of the concordance between real-time polymerase chain reaction (PCR) and NGS on formalin-fixed paraffin-embedded (FFPE) for simultaneous detection and genotyping of HPV-HR at diagnosis(Inclusion)
- Number of patients with ctDNA and cvDNA detection at diagnosis and the clinical, paraclinical and pathological features of the cancer(Through study completion, an average of 66 months)
- Evaluation of interobserver reproducibility of the interpretation of SUVmax measurements of residual cervical adenomegaly.(3 months after potentiated radiotherapy)
- Test of the concordance between real-time polymerase chain reaction (PCR) and NGS on formalin-fixed paraffin-embedded (FFPE) for simultaneous detection and genotyping of HPV-HR at diagnosis(Inclusion)
- Assessment of the prognosis value of the presence of residual adenomegaly(At month 27)
- cDNA detection rate among patients with residual adenomegaly after treatment(at three-months after potentiated radiotherapy.)
- Assessment of the prognostic value of cDNA detection 3 months after the end of radiochemotherapy for patients with residual adenomegaly(at three-months after potentiated radiotherapy.)
- Evaluation of interobserver reproducibility of the interpretation of SUVmax measurements of residual cervical adenomegaly.(3 months after potentiated radiotherapy)
- Rate of concordance of mutational profiles and Human papillomavirus-high risk (HPV-HR) genotypes between the primary tumor and cDNAs at diagnosis(Inclusion)
- Rate of concordance between p16 immunohistochemistry and HPV-HR genotyping on the primary tumor(Inclusion)
- Number of patients with ctDNA and cvDNA detection at diagnosis and the clinical, paraclinical and pathological features of the cancer(Through study completion, an average of 66 months)